Authors: | Kunig, Verena B. K. Potowski, Marco Klika Škopić, Mateja Brunschweiger, Andreas |
Title: | Scanning protein surfaces with DNA-encoded libraries |
Language (ISO): | en |
Abstract: | Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug-like compounds on any site, can give important stimuli to drug-development projects. For instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA-encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein-coupled receptors (GPCRs) and kinases. The protein surface-binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small-molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target-focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment-like, starting points. |
Subject Headings: | DNA-encoded libraries Drug development Peptidomimetics Protein-protein interactions Screening |
URI: | http://hdl.handle.net/2003/40885 http://dx.doi.org/10.17877/DE290R-22742 |
Issue Date: | 2020-12-09 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Medizinische Chemie und Chemische Biologie |
Files in This Item:
File | Description | Size | Format | |
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ChemMedChem - 2020 - Kunig - Scanning Protein Surfaces with DNA‐Encoded Libraries.pdf | DNB | 7.03 MB | Adobe PDF | View/Open |
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